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Tests for Smell Loss May Detect Alzheimer’s and PD

Image: Smell problems can increase people’s risk for health-related conditions and can also be a sign of neurodegenerative disease (Photo courtesy of Getty Images).

In a new approach to testing for olfaction dysfunction, researchers have developed “white smells,” mixtures of several odor molecules, which help reduce test bias and patient subjectivity, thus also creating a more globally applicable testing format. They suggest that these tests could also aid in earlier detection of neurological disorders that have been associated with olfaction problems.

The sense of smell is often taken for granted, until it malfunctions. Researchers at Rockefeller University (New York City, NY, USA) are developing a new type of test to help improve diagnosis of smell disorders and of associated diseases that can be detected with smell tests.

“People have their vision and hearing tested throughout their lives, but smell testing is exceedingly rare,” said Leslie Vosshall, who professor at Rockefeller U. and a Howard Hughes Medical Institute investigator, and who developed the new test format with Julien Hsieh, a Rockefeller clinical scholar who’s now a resident at the Geneva University Hospitals (Switzerland), and colleagues.

One problem with current tests for smell limitations is that they rely on a patient’s ability to detect and identify (name) single types of odor molecules, such as rose-scented phenylethyl alcohol. However, the ability to detect odors and to recognize them can vary greatly between people. Someone with an otherwise normal sense of smell may not be able to detect the rose molecule, while another person who can smell roses but is from an area where these flowers are scarce may struggle to put a name to the scent. In either case, there is the potential for misdiagnosis, particularly when testing across different populations and regions.

The researchers set out to eliminate these potential biases with the help of “white smells,” named based on conceptual similarity to “white light” as combination of wavelengths of light, and “white noise” as combination of many frequencies of sound. They prepared “white smells” by mixing many odors together to produce something unfamiliar, from assortments of 30 different odor molecules.

Their two new tests ask patients to distinguish white smells with overlapping ingredients and to detect white smells at increasingly lower concentrations. If a person is unable to detect a single component of the test scent, this has little effect on the result. Furthermore, test-takers do not need to identify the odor at all: “[The tests] focus on the problem of smell itself, because they don’t force people to match smells to words,” said Prof. Vosshall.

In clinical trials conducted at Rockefeller University Hospital (NY, USA) and Taichung Veterans General Hospital (Taiwan), the new tests detected smell loss more reliably than conventional options. The results open up the possibility of a better means to detect smell loss, and even to aid in detection of Alzheimer’s and Parkinson’s diseases by using “changes in the sense of smell, along with other biomarkers, to identify underlying causes of these neurological disorders very early, and so potentially improve treatment,” said Dr. Hsieh.

The study, by Hsieha JW et al, was published October 10, 2017, in the journal Proceedings of the National Academy of Sciences (PNAS).